N,N-disubstituted aminoalkylbiphenyl antagonists of prostaglandin D2 receptors

Abstract

Described herein are compounds that are antagonists of PGD 2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein that are antagonists of PGD 2 receptors. Also described herein are methods of using such antagonists of PGD 2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD 2 -dependent or PGD 2 -mediated conditions or diseases.

1. A compound having the structure of Formula (I), or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
       
       wherein,
 Q is tetrazolyl or —C(═O)-Q′;
 Q 1  is —OH, —O(C 1 -C 4 alkyl), —NHSO 2 R 12 , —N(R 13 ) 2 , —NH—OH, or —NH—CN; 
 
 each R 1  is independently selected from H, F, and —CH 3 ; 
 each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 9  is independently H, halogen, —CN, —NO 2 , —OH, —OR 13 , —SR 12 , —S(═O)R 12 , —S(═O) 2 R 12 , —NHS(═O) 2 R 12 , —C(═O)R 12 , —OC(═O)R 12 , —CO 2 R 13 , —OCO 2 R 13 , —CH(R 13 ) 2 , —N(R 13 ) 2 , —NHCH 2 CO 2 R 13 , —OCH 2 CO 2 R 13 , —SCH 2 CO 2 R 13 , —C(═O)N(R 13 ) 2 , —OC(═O)N(R 13 ) 2 , —NHC(═O)NH(R 13 ), —NHC(═O)R 12 , —NHC(═O)OR 12 , —C(OH)(R 13 ) 2 , C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 1 -C 6 alkoxy, C 1 -C 6 heteroalkyl, C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted monocyclic heteroaryl, or a substituted or unsubstituted bicyclic heteroaryl, —OCH 2 —(C 3 -C 6 cycloalkyl), —OCH 2 —(substituted or unsubstituted phenyl), or —OCH 2 —(substituted or unsubstituted monocyclic heteroaryl); 
 R 10  —C(═O)R 14 , —C(═O)OR 15 , —C(═O)N(R 16 ) 2 , —C(═NR 19 )N(R 16 ) 2 , —S(═O) 2 N(R 16 ) 2  or —S(═O) 2 R 15 ;
 R 14  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-(C 3 -C 10 cycloalkyl), —C 1 -C 4 alkyl-(a substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(a substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(a substituted or unsubstituted heteroaryl); or 
 R 14  is L 3 -X 3 -Q 3 ;
 L 3  is a C 1 -C 4 alkylene; 
 X 3  is a bond, —O—, —S—, —S(═O)—, —S(═O) 2 —, or —NR 13 —; 
 Q 3  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-C 3 -C 10 cycloalkyl, —C 1 -C 4 alkyl-(a substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(a substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(a substituted or unsubstituted heteroaryl); 
 
 R 15  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 10  cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-C 3 -C 10 cycloalkyl, —C 1 -C 4 alkyl-(substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl); 
 each R 16  is independently H, —CN, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-C 3 -C 10 cycloalkyl, —C 1 -C 4 alkyl-(substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl); or 
 two R 16  groups attached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted heterocycloalkyl; 
 R 19  is selected from among H, —S(═O) 2 R 12 , —S(═O) 2 NH 2 , —C(═O)R 12 , —CN, and —NO 2 ; 
 R 11  is C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, —C 1 -C 6 alkylene-OH, —C 1 -C 6 alkylene-O—(C 1 -C 4 alkyl), —C 1 -C 6 alkylene-S—(C 1 -C 4 alkyl), —C 1 -C 4 alkylene-S(═O)—(C 1 -C 4 alkyl), —C 1 -C 6 alkylene-S(═O) 2 —(C 1 -C 4 alkyl), —C 1 -C 6 alkylene-NH 2 , —C 1 -C 6 alkylene-N(CH 3 ) 2 , —C 1 -C 6 alkylene-C(═O)—(C 1 -C 4 alkyl), —C 1 -C 6 alkylene-C(═O)OH, —C 1 -C 6 alkylene-C(═O)O(C 1 -C 4 alkyl), or —C 1 -C 6 alkylene-C(═O)NH 2 ; 
 R 12  is C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 -fluoroalkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted benzyl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-(substituted or unsubstituted C 3 -C 10 cycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl); 
 each R 13  is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 -fluoroalkyl, a substituted or unsubstituted C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted benzyl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-(substituted or unsubstituted C 3 -C 10 cycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), and —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl); or 
 two R 13  groups attached to the same N atom are taken together with the N atom to which they are attached to form an optionally substituted C 2 -C 10 heterocycloalkyl. 
 
 
     
     
       2. The compound of  claim 1 , or a pharmaceutically acceptable salt thereof, wherein:
 Q is —C(═O)-Q 1 ; 
 Q 1  is —OH, or —O(C 1 -C 4 alkyl); 
 at least one of R 2  and R 3  is H; 
 at least two of R 6 , R 7  and R 9  is H; 
 R 11  is C 1 -C 6 alkyl, C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, —C 1 -C 6 alkylene-C(═O)OH, —C 1 -C 6 alkylene-C(═O)O(C 1 -C 4 alkyl), or —C 1 -C 6 alkylene-C(═O)NH 2 . 
 
     
     
       3. The compound of  claim 2 , or a pharmaceutically acceptable salt thereof, wherein:
 each R 1  is H; 
 each of R 2 , R 3 , R 6 , R 7  and R 9  is independently selected from H, halogen, —OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, and C 1 -C 4 -fluoroalkyl; 
 R 4  is H, F, Cl, Br, I, —CN, —OH, —C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 1 -C 6 alkoxy, C 1 -C 6 heteroalkyl, —OCH 2 —CO 2 R 13 , OCH 2 —C 3 -C 6 cycloalkyl, or —OCH 2 — (substituted or unsubstituted phenyl); 
 R 5  is H, halogen, —CN, —NO 2 , —OH, —OR 13 , —SR 12 , —S(═O)R 12 , —S(═O) 2 R 12 , —NHS(═O) 2 R 12 , —C(═O)R 12 , —OC(═O)R 12 , —CO 2 R 13 , —OCO 2 R 13 , —CH(R 13 ) 2 , —N(R 13 ) 2 , —NHCH 2 CO 2 R 13 , —OCH 2 CO 2 R 13 , —SCH 2 CO 2 R 13 , —C(═O)N(R 13 ) 2 , —OC(═O)N(R 13 ) 2 , —NHC(═O)NH(R 13 ), —NHC(═O)R 12 , —NHC(═O)OR 12 , —C(OH)(R 13 ) 2 , —C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, C 1 -C 6 -fluoroalkoxy, C 1 -C 6 alkoxy, C 1 -C 6 heteroalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted monocyclic heteroaryl, substituted or unsubstituted bicyclic heteroaryl; 
 R 10  is —C(═O)R 14 , —C(═O)OR 15 , or —C(═O)N(R 16 ) 2 ;
 R 14  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, or C 3 -C 6 cycloalkyl; or 
 R 14  is L 3 -X 3 -Q 3 ;
 L 3  is a C 1 -C 4 alkylene; 
 X 3  is a bond, —O—, —S—, —S(═O)—, —S(═O) 2 —, or —NR 13 —; 
 Q 3  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 3 -C 10 cycloalkyl, a substituted or unsubstituted C 2 -C 10 heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-C 3 -C 10 cycloalkyl, —C 1 -C 4 alkyl-(a substituted or unsubstituted C 2 -C 10 heterocycloalkyl), —C 1 -C 4 alkyl-(a substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(a substituted or unsubstituted heteroaryl); 
 
 R 15  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 10  cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-C 3 -C 10 cycloalkyl, —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl); 
 each R 16  is independently H, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 10 cycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, —C 1 -C 4 alkyl-(C 3 -C 10 cycloalkyl), —C 1 -C 4 alkyl-(substituted or unsubstituted aryl), or —C 1 -C 4 alkyl-(substituted or unsubstituted heteroaryl). 
 
 
     
     
       4. The compound of  claim 3 , or a pharmaceutically acceptable salt thereof, wherein:
 each of R 6 , R 7  and R 9  are H; 
 R 10  is —C(═O)R 14 , —C(═O)OR 15 , or —C(═O)N(R 16 ) 2 ;
 R 14  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, or C 3 -C 6 cycloalkyl; or 
 R 14  is L 3 -X 3 -Q 3 ;
 L 3  is —CH 2 —, —CH(CH 3 )—, or —C(CH 3 ) 2 —; 
 X 3  is a —O—, —S—, —S(═O)—, —S(═O) 2 —, or —NR 13 —; 
 Q 3  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted monocyclic heteroaryl, —CH 2 — (a substituted or unsubstituted phenyl), or —CH 2 — (a substituted or unsubstituted monocyclic heteroaryl); 
 
 R 15  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted monocyclic heteroaryl, —CH 2 —C 3 -C 6 cycloalkyl, —CH 2 — (substituted or unsubstituted phenyl), —CH(CH 3 )-(substituted or unsubstituted phenyl), —CH 2 — (substituted or unsubstituted monocyclic heteroaryl) or —CH(CH 3 )-(substituted or unsubstituted monocyclic heteroaryl); 
 each R 16  is independently H, C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 heteroalkyl, C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, a substituted or unsubstituted monocyclic heteroaryl, —CH 2 —(C 3 -C 6 cycloalkyl), —CH 2 — (a substituted or unsubstituted phenyl), —CH(CH 3 )-(a substituted or unsubstituted phenyl), —CH 2 — (a substituted or unsubstituted monocyclic heteroaryl), or —CH(CH 3 )-(a substituted or unsubstituted monocyclic heteroaryl). 
 
 
     
     
       5. The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of Formula (III): 
       
         
           
           
               
               
           
         
       
     
     
       6. The compound of  claim 5 , or a pharmaceutically acceptable salt thereof, wherein:
 R 14  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, or C 3 -C 6 cycloalkyl; or 
 R 14  is L 3 -X 3 -Q 3 ;
 L 3  is —CH 2 —, —CH(CH 3 )—, or —C(CH 3 ) 2 —; 
 X 3  is —O—, —S—, —S(═O)—, or —S(═O) 2 —; 
 Q 3  is C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 3 -C 6 cycloalkyl, a substituted or unsubstituted phenyl, or —CH 2 — (a substituted or unsubstituted phenyl); 
 
 R 11  is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 6 cycloalkyl. 
 
     
     
       7. The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of Formula (IV): 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound of  claim 7 , or a pharmaceutically acceptable salt thereof, wherein:
 R 15  is C 1 -C 6 alkyl, —CH 2 — (substituted or unsubstituted phenyl), —CH(CH 3 )-(substituted or unsubstituted phenyl), —CH 2 — (substituted or unsubstituted monocyclic heteroaryl) or —CH(CH 3 )-(substituted or unsubstituted monocyclic heteroaryl); 
 R 11  is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 6 cycloalkyl. 
 
     
     
       9. The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein the compound has the structure of Formula (V): 
       
         
           
           
               
               
           
         
       
     
     
       10. The compound of  claim 9 , or a pharmaceutically acceptable salt thereof, wherein:
 one R 16  is H and the other R 16  is —CH 2 — (a substituted or unsubstituted phenyl), —CH(CH 3 )-(a substituted or unsubstituted phenyl), —CH 2 — (a substituted or unsubstituted monocyclic heteroaryl), or —CH(CH 3 )-(a substituted or unsubstituted monocyclic heteroaryl); 
 R 11  is C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 3 -C 6 cycloalkyl. 
 
     
     
       11. The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein:
 R 2  and R 3  are H; 
 R 4  is H, F, Cl, Br, I, —CN, —OH, —C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 1 -C 6 alkoxy, or C 1 -C 6 heteroalkyl; 
 R 5  is F, Cl, Br, I, —CN, —NO 2 , —OH, —CH 3 , —CH 2 CH 3 , i-propyl, -tBu, —CF 3 , —CH 2 CF 3 , —OCH 3 , —OCF 3 , —C(CH 3 ) 2 OH, —C(CH 2 CH 3 ) 2 OH, —S(═O) 2 (C 1 -C 6 alkyl), —S(═O) 2 (substituted or unsubstituted phenyl), —NHS(═O) 2 (C 1 -C 6 alkyl), —NHS(═O) 2 (substituted or unsubstituted phenyl), —NHS(═O) 2 (substituted or unsubstituted heteroaryl), —C(═O)-(substituted or unsubstituted phenyl), —C(═O)CH 3 , —CO 2 H, —CO 2 CH 3 , —CO 2 CH 2 CH 3 , —NH 2 , —C(═O)NH 2 , —C(═O)NH(CH 3 ), —C(═O)NH(CH 2 CH 3 ), —C(═O)NH(tBu), —C(═O)NH(iPr), —C(═O)NH(CH 2 CF 3 ), —C(═O)NH(CH 2 CH 2 OCH 3 ), —C(═O)NH(substituted or unsubstituted phenyl), —C(═O)NH(substituted or unsubstituted monocyclic heteroaryl), —NHC(═O)(C 1 -C 6 alkyl), —NHC(═O)(substituted or unsubstituted phenyl), —NHC(═O)(substituted or unsubstituted monocyclic heteroaryl), —NHC(═O)NH 2 , or —NHC(═O)NH(substituted or unsubstituted phenyl). 
 
     
     
       12. The compound of  claim 4 , or a pharmaceutically acceptable salt thereof, wherein:
 R 2  and R 3  are H; 
 R 4  is H, F, Cl, Br, I, —CN, —OH, —C 1 -C 6 alkyl, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 1 -C 6 alkoxy, or C 1 -C 6 heteroalkyl; 
 R 5  is C 3 -C 10 cycloalkyl, substituted or unsubstituted C 2 -C 10 heterocycloalkyl, substituted or unsubstituted phenyl, substituted or unsubstituted napthyl, substituted or unsubstituted monocyclic heteroaryl, or substituted or unsubstituted bicyclic heteroaryl. 
 
     
     
       13. The compound of  claim 5 , or a pharmaceutically acceptable salt thereof, wherein
 R 2  and R 3  are H; 
 R 4  is H, F, Cl, Br, —OH, —CH 3 , —OCH 3 , —CF 3 , or —OCF 3 ; 
 R 5  is a substituted or unsubstituted group selected from pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, isoxazolyl, isothiazolyl, pyridinyl, pyridazinyl, pyrazinyl, pyrimidinyl, quinolinyl, and isoquinolinyl; 
 R 11  is —CH 3 , —CH 2 CH 3 , or —CH 2 CF 3 . 
 
     
     
       14. A compound selected from:
 {2′-[(Acetyl-methyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Acetyl-(2,2-dimethyl-propyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Acetyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Acetyl-(2-hydroxy-ethyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Acetyl-(2-methoxy-ethyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Acetyl-(2-dimethylamino-ethyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[(Acetyl-carboxymethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-carbamoylmethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Acetyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Acetyl-cyclopropyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[((S)-Acetyl-indan-1-yl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[((R)-Acetyl-indan-1-yl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Acetyl-((1R,2S)-2-hydroxy-indan-1-yl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-[Acetyl-((1R,2S)-2-methoxy-indan-1-yl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Acetyl-indan-2-yl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-phenyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-benzyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-phenethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; 2-{2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; {2′41-(Acetyl-ethyl-amino)-ethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Ethyl-methoxycarbonyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyl-methoxycarbonyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {6-Methoxy-2′-[(methoxycarbonyl-phenethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Indan-2-yl-methoxycarbonyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-methyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-methyl-amino)-methyl]-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-cyclobutyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-cyclopentyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(2,2,2-trifluoro-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid (Compound 132); {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid (Compound 133); {2′-[(Benzyloxycarbonyl-cyclobutyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-cyclopentyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-cyclopropyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; 2-carboxylic acid; (2′-{[(3,5-Dichloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[(2-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[(3,5-Difluoro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-[(4-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[(3-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-({[1-(4-Chloro-phenyl)-ethoxycarbonyl]-ethyl-amino}-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; (2′-{[Ethyl-(2-phenoxy-propionyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(2-methoxy-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[3-(2-Bromo-phenyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(2-phenoxy-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Benzyloxycarbonyl-(2,2,2-trifluoro-ethyl)-amino]-methyl}-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4′-bromo-6-methoxy-biphenyl-3-yl}-acetic acid; {4′-Acetylamino-2′-[(acetyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-pyrazol-1-yl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-o-tolyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-thiazol-2-yl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid (Compound 154); (2′-{[Acetyl-(2-methyl-pyrimidin-4-yl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methyl-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-methyl-amino)-methyl]-6-fluoro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-methyl-amino)-methyl]-6-methyl-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-cyclopropyl-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4-methyl-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-methyl-amino)-methyl]-4′-bromo-6-methoxy-biphenyl-3-yl}-acetic acid; {4′-Acetylamino-2′-[(acetyl-methyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-methoxycarbonylamino-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4′-methanesulfonylamino-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4′-methanesulfonyl-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-pyrrolidin-1-yl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-methyl-amino)-methyl]-6-methoxy-4′-pyrazol-1-yl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4′-cyclopropyl-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-[1,1′;4′,1″]terphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-oxazol-2-yl-biphenyl-3-yl}-acetic acid; [2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-(1H-pyrazol-4-yl)-biphenyl-3-yl]-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-pyridin-2-yl-biphenyl-3-yl}-acetic acid; {2′-[(Cyclopropoxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; [2′-(1-Ethyl-3-methyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Cyclopropanecarbonyl-methyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid (Compound 177); {2′-[(Cyclopentanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzoyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(pyridine-2-carbonyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(pyrazine-2-carbonyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(1-methyl-1H-pyrazole-3-carbonyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-5′-bromo-6-methoxy-biphenyl-3-yl}-acetic acid; {5′-Acetylamino-2′-[(acetyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-5′-methoxycarbonylamino-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-5′-methanesulfonylamino-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-5′-pyrrolidin-1-yl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-5′-pyrazol-1-yl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-3′-methanesulfonyl-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-difluoro-acetic acid; (2′-{[(2-Benzyloxy-acetyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-({[2-(4-Chloro-phenoxy)-acetyl]-ethyl-amino}-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1,3-diethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; (2′-{[Ethyl-(pyrrolidine-1-carbonyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; 2-{2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; [2′-(3-Cyano-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid (Compound 199); (2′-{[(4-Chloro-benzenesulfonyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Methanesulfonyl-phenethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Acetyl-((1S,2R)-2-hydroxy-1-methyl-2-phenyl-ethyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-5-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; [2′-(N′-Benzyl-N″-cyano-N-ethyl-guanidinomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(N′-Cyano-N″-cyclohexylmethyl-N-ethyl-guanidinomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[N′-Cyano-N″-(2,2-dimethyl-propyl)-N-ethyl-guanidinomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[N′-Cyano-N-ethyl-N″-(4-methoxy-benzyl)-guanidinomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; 2-{2′-[(Acetyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-2-methyl-propionic acid; 2-{2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-2-methyl-propionic acid; (2′-{[Ethyl-(2-phenylsulfanyl-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-({[2-(4-Chloro-phenoxy)-2-methyl-propionyl]-ethyl-amino}-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; (2′-{[(2-Benzenesulfinyl-acetyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-[(2-Benzenesulfonyl-acetyl)-ethyl-amino]-methyl 1-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-(1-Ethyl-3-phenyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6′-methoxy-biphenyl-3-yl}-acetic acid (2′-{[(3,5-Difluoro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6′-methoxy-biphenyl-3-yl)-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-5-fluoro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4-fluoro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {6-Benzyloxy-2′-[(benzyloxycarbonyl-ethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-ethoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-cyclopropylmethoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; [2′-({[1-(2,4-Dichloro-phenyl)-cyclopropanecarbonyl]-ethyl-amino}-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-difluoro-acetic acid; {5-Chloro-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-5-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; [2′-(1-Ethyl-3-pyridin-2-ylmethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′43-(4-Chloro-benzyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2″-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4″-trifluoromethyl-[1,1′;2′,1″]terphenyl-4′-yl}-acetic acid; [2′-(N′-Cyano-N-ethyl-N″-propyl-guanidinomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(N′-Cyano-N″-cyclopropylmethyl-N-ethyl-guanidinomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(N′-Cyano-N-ethyl-N″-pyridin-2-ylmethyl-guanidinomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; (2′-{[Ethyl-(2-pyrazol-1-yl-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-({Ethyl-[2-(2-methyl-imidazol-1-yl)-acetyl]-amino}-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; (2′-[Ethyl-(2-[1,2,4]triazol-1-yl-acetyl)-amino]-methyl-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(2-pyrrolidin-1-yl-acetyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[3-(3,4-Dichloro-benzyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {4′-Acetylamino-2′-[(benzyloxycarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid; [2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-(4-chloro-benzoylamino)-6-methoxy-biphenyl-3-yl]-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-methanesulfonylamino-6-methoxy-biphenyl-3-yl}-acetic acid; [2′-4(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-(4-chloro-benzenesulfonylamino)-6-methoxy-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-5-chloro-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-5-fluoro-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Ethyl-methoxycarbonyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-acetic acid; {5-Chloro-2′-[(ethyl-methoxycarbonyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[3-(3,5-Dichloro-benzyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl}-6-methoxy-5′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl}-6-methoxy-5′-methyl-biphenyl-3-yl)-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-5′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-5′-methyl-biphenyl-3-yl}-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-5′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-5′-methyl-biphenyl-3-yl]-acetic acid; (2′-{[(4-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-5′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[(4-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6-methoxy-5′-methyl-biphenyl-3-yl)-acetic acid; {2′-[1-Ethyl-3-(4-fluoro-benzyl)-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[3-(3-Chloro-benzyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[3-(3,5-Difluoro-benzyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{3-[(R)-1-(4-Chloro-phenyl)-ethyl]-1-ethyl-ureidomethyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{3-[(S)-1-(4-Chloro-phenyl)-ethyl]-1-ethyl-ureidomethyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; [2′-(1,3-Diethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(3-Cyclopropyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-fluoro-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Acetyl-ethyl-amino)-methyl]-4′-fluoro-6-methoxy-biphenyl-3-yl]-acetic acid; {2′-[3-(4-Chloro-benzyl)-1-ethyl-ureidomethyl]-4′-fluoro-6-methoxy-biphenyl-3-yl}-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-fluoro-6-methoxy-biphenyl-3-yl}-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-4′-fluoro-6-methoxy-biphenyl-3-yl]-acetic acid; (5-Chloro-2′-[(4-chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-[(4-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-acetic acid; (5-Chloro-2′-{[ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl}-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-[Ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl}-5,4′-bis-trifluoromethyl-biphenyl-3-yl)-acetic acid (Compound 1191); {5-Chloro-2′-[3-(4-chloro-benzyl)-1-ethyl-ureidomethyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[3-(4-Chloro-benzyl)-1-ethyl-ureidomethyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(4-fluoro-benzyloxycarbonyl)-amino]-methyl}-6,5′-dimethoxy-biphenyl-3-yl)-acetic acid; (2′-[(4-Chloro-benzyloxycarbonyl)-ethyl-amino]-methyl}-6,5′-dimethoxy-biphenyl-3-yl)-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6,5′-dimethoxy-biphenyl-3-yl}-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6,5′-dimethoxy-biphenyl-3-yl]-acetic acid; [2′-(1-Ethyl-3-pyridin-3-ylmethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid (Compound 1198); [2′-(1-Ethyl-3-pyridin-4-ylmethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[3-(6-Chloro-pyridin-3-ylmethyl)-1-ethyl-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; [5-Chloro-2′-(1-ethyl-3-methyl-ureidomethyl)-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [2′-(1-Ethyl-3-methyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-acetic acid; {2′-[(Benzoyl-ethyl-amino)-methyl]-5-chloro-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Benzoyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Cyclobutanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[(Ethyl-phenylacetyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[Ethyl-(3-phenyl-propionyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; (2′-{[Ethyl-(1-hydroxy-cyclopropanecarbonyl)-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(1-Ethyl-ureido)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; 2-{2′-[(Acetyl-ethyl-amino)-methyl]-5-chloro-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; 2-{5-Chloro-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; 2-{2′-[(Acetyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-propionic acid; 2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-propionic acid; {2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-methanesulfonyl-6-methoxy-biphenyl-3-yl}-acetic acid; [2′-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-4′-(1-hydroxy-1-methyl-ethyl)-6-methoxy-biphenyl-3-yl)-acetic acid; 2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; {5-Chloro-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-5′-methoxy-biphenyl-3-yl}-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-5-chloro-5′-methoxy-biphenyl-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-hydroxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid; [5-Chloro-2′-({[2-(4-chloro-phenoxy)-acetyl]-ethyl-amino]-methyl)-5′-methoxy-biphenyl-3-yl}-acetic acid; 2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-propionic acid; 2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-5-chloro-4′-trifluoromethyl-biphenyl-3-yl]-propionic acid; (R)-2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; (S)-2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-propionic acid; 2-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-5′-carboxymethyl-2′-methoxy-biphenyl-4-carboxylic acid; [2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphen-3-yl]-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-4′-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid; [2′-({[2-(4-Chloro-phenoxy)-acetyl]-ethyl-amino}-methyl)-4′-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-quinolin-7-yl-biphenyl-3-yl}-acetic acid (Compound 1230); [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-quinolin-7-yl-biphenyl-3-yl]-acetic acid; [2′-({[2-(4-Chloro-phenoxy)-acetyl]-ethyl-amino}-methyl)-6-methoxy-4′-quinolin-7-yl-biphenyl-3-yl]-acetic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-(1-methyl-1H-pyrazol-4-yl)-biphenyl-3-yl}-acetic acid; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-(1-methyl-1H-pyrazol-4-yl)-biphenyl-3-yl]-acetic acid; 2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-2-methyl-propionic acid; (R)-2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-propionic acid; (S)-2-{2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-5,4′-bis-trifluoromethyl-biphenyl-3-yl}-propionic acid; (R)-2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-propionic acid; (S)-2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-propionic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-methylsulfanyl-biphenyl-3-yl}-acetic acid; {5-Chloro-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-methylsulfanyl-biphenyl-3-yl}-acetic acid; 2-[2′-(3-Cyclopropyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-propionic acid; {2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; (2′-{[(2,2-Dimethyl-propionyl)-ethyl-amino]-methyl}-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl)-acetic acid; {2′-[(Ethyl-isobutyryl-amino)-methyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid (Compound 1216); {4′-Bromo-2′-[(cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid; [2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-4′-(5-fluoro-pyridin-2-yl)-6-methoxy-biphenyl-3-yl]-acetic acid; [2′-[(Cyclopropanecarbonyl-ethyl-amino)-methyl]-6-methoxy-4′-(5-methoxy-pyrimidin-2-yl)-biphenyl-3-yl]-acetic acid; {2′-[1-Ethyl-3-(4-hydroxy-benzyl)-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; {2′-[1-Ethyl-3-(2-hydroxy-benzyl)-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; [2′-[(Benzoyl-ethyl-amino)-methyl]-4′-(6-ethoxy-pyridin-3-yl)-6-methoxy-biphenyl-3-yl]-acetic acid; {4′-(6-Ethoxy-pyridin-3-yl)-2′-[(ethyl-phenylacetyl-amino)-methyl]-6-methoxy-biphenyl-3-yl}-acetic acid (Compound 1255); (4′-(6-Ethoxy-pyridin-3-yl)-2′-{[ethyl-(3-phenyl-propionyl)-amino]-methyl}-6-methoxy-biphenyl-3-yl)-acetic acid (Compound 1256); {2′-[1-Ethyl-3-(3-hydroxy-benzyl)-ureidomethyl]-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl}-acetic acid; N-Ethyl-N-[5′-(2-methanesulfonylamino-2-oxo-ethyl)-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl]-acetamide (Compound 21); N-Ethyl-N-[5′-(2-hydroxy-2-methyl-propyl)-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl]-acetamide; Cyclopropanecarboxylic acid (5′-cyanomethyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-ethyl-amide; (5′-Cyanomethyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-ethyl-carbamic acid benzyl ester; Ethyl-[2′-methoxy-5′-(2H-tetrazol-5-ylmethyl)-4-trifluoromethyl-biphenyl-2-ylmethyl]-carbamic acid benzyl ester; (5′-Carbamoylmethyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-ethyl-carbamic acid benzyl ester; Cyclopropanecarboxylic acid ethyl-[2′-methoxy-5′-(2H-tetrazol-5-ylmethyl)-4-trifluoromethyl-biphenyl-2-ylmethyl]-amide; Cyclopropanecarboxylic acid (5′-carbamoylmethyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-ethyl-amide; [2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-hydroxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic acid ethyl ester; (R)-2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-N—((R)-1-methyl-2-phenyl-ethyl)-propionamide (Compound 210); (S)-2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-5,4′-bis-trifluoromethyl-biphenyl-3-yl]-N—((R)-1-methyl-2-phenyl-ethyl)-propionamide; Cyclopropanecarboxylic acid ethyl-{2′-methoxy-5′-[(R)-1-methyl-2-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-2-oxo-ethyl]-4-trifluoromethyl-biphenyl-2-ylmethyl}-amide; Cyclopropanecarboxylic acid ethyl-{2′-methoxy-5′-[(S)-1-methyl-2-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-2-oxo-ethyl]-4-trifluoromethyl-biphenyl-2-ylmethyl}-amide; 2-[(Benzyloxycarbonyl-ethyl-amino)-methyl]-5′-ethoxycarbonylmethyl-2′-methoxy-biphenyl-4-carboxylic acid; Cyclopropanecarboxylic acid ethyl-{3′-[(R)-1-methyl-2-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-2-oxo-ethyl]-4,5′-bis-trifluoromethyl-biphenyl-2-ylmethyl}-amide; Cyclopropanecarboxylic acid ethyl-{3′-[(S)-1-methyl-2-((4R,5S)-4-methyl-2-oxo-5-phenyl-oxazolidin-3-yl)-2-oxo-ethyl]-4,5′-bis-trifluoromethyl-biphenyl-2-ylmethyl}-amide; and (2S,3S,4S,5R,6S)-6-{2-[2′-(3-Benzyl-1-ethyl-ureidomethyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetoxy}-3,4,5-trihydroxy-tetrahydro-pyran-2-carboxylic acid; or a pharmaceutically acceptable salt thereof. 
 
     
     
       15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable inactive ingredient selected from pharmaceutically acceptable diluents, pharmaceutically acceptable excipients, and pharmaceutically acceptable carriers. 
     
     
       16. The pharmaceutical composition of  claim 15 , wherein the pharmaceutical composition is formulated for intravenous injection, oral administration, inhalation, nasal administration, topical administration, ophthalmic administration or otic administration. 
     
     
       17. The pharmaceutical composition of  claim 15 , wherein the pharmaceutical composition is a tablet, a pill, a capsule, a liquid, an inhalant, a nasal spray solution, a suppository, a suspension, a gel, a colloid, a dispersion, a suspension, a solution, an emulsion, an ointment, a lotion, an eye drop or an ear drop. 
     
     
       18. A method for treating allergic rhinitis, allergic conjuctivitis, or sinusitis, in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
       19. The compound of  claim 9 , or a pharmaceutically acceptable salt thereof, wherein:
 R 2  and R 3  are H; 
 R 4  is H, F, Cl, Br, —OH, —CH 3 , —OCH 3 , —CF 3 , or —OCF 3 ; 
 R 5  is F, Cl, Br, —OH, —CH 3 , —CF 3 , —OCH 3 , or —OCF 3 ; 
 R 11  is —CH 3 , —CH 2 CH 3 , or —CH 2 CF 3 ; 
 one R 16  is H and the other R 16  is —CH 2 — (a substituted or unsubstituted phenyl). 
 
     
     
       20. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       21. The compound of  claim 20 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
       22. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       23. The compound of  claim 22 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
       24. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       25. The compound of  claim 24 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
       26. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       27. The compound of  claim 26 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
       28. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       29. The compound of  claim 28 , wherein the pharmaceutically acceptable salt is a sodium salt. 
     
     
       30. The compound of  claim 1 , wherein the compound has the structure: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
       31. The compound of  claim 30 , wherein the pharmaceutically acceptable salt is a sodium salt.